Malaria, a blood disease of humans, is responsible for 96 million cases annually; in Africa alone malaria is reported to be responsible for a million deaths. Much effort has been expended to eradicate this disease, but success has been elusive for a variety of reasons: appearance of parasite strains that are resistant to what were once effective antimalarials, the development of vector resistance to insecticides, the absence of an effective vaccine and economic constraints. One of the logical approaches toward providing effective chemoprophyllaxis and treatment of malaria is to develop new drugs that will specifically inhibit parasite growth and reproduction. Development of such a drug arsenal could come from a variety of established procedures, and would be considerably facilitated by a more complete understanding of the biochemical differences that may exist between the intracellular plasmodium and its host. The proposed program of research is designed to provide such essential and basic information by studying: 1) The mechanisms of purine transport by the erythrocytic stages of the human malaria, Plasmodium falciparum, 2) The metabolic conversions of purines, nucleosides and nucleotides that take place both in the red cell and in the parasite during its development, 3) The purine salvage pathway enzymes of P. falciparum, 4) The possible role exogenous purine nucleobases and nucleosides may play in improving the in vitro growth of the parasite and in promoting ssynchronous intraerythrocytic development and 5) The effectiveness of antimalarial drugs that affect parasite utilization of purines in vitro. Comparative studies of purine metabolism will be made using the exoerythrocytic stages of the avian malarias P. lophurae or P. fallax. Standard isotopic and enzymatic techniques will be used to follow transport and metabolic pathways. In vitro cultures of the erythrocytic stages of P. falciparum will be maintained by the Trager-Jensen method; exoerythrocytic stages of malaria will be grown using the techniques of Davis et al.